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ABSTRACT: Several studies of South American populations showed that altitude is associated with low birth weight and intrauterine growth retardation. Although some of them analyzed the altitude-birth weight association, only a few assessed the effect of the interaction between altitude and socioeconomic factors on birth weight. The purpose of this research is to evaluate such effects on birth weight, after adjustment for confounding factors. This observational descriptive study includes a sample of 37,022 live-born infants without congenital anomalies, weighing >or=500 g, from 75 South American maternity hospitals, during 1982-1999. Of the total sample, 1,187 infants were born in two South American cities located at more than 2,000-m altitude: La Paz, Bolivia (N = 974 at 3,600 m) and Bogota, Colombia (N = 274 at 2,600 m). Among the seven risk factors analyzed, altitude was the main predictor of birth weight (except for gestational age). After adjustment for the other risk factors, birth weight at cities located above 2,000 m showed a decrease of approximately 200 g. When comparing highest and lowest socioeconomic levels, birth weight also showed differences for levels of altitude analyzed (lowland, <2,000 m; middle land, 2,600 m; and highland, 3,600 m). Interaction between both factors showed no effect. High altitude seems to act independent of socioeconomic status in explaining birth weight reduction.